1. Technical Field
The present invention generally relates to an amorphous bupropion hydrobromide, processes for preparation thereof, and stable pharmaceutical compositions therewith.
The present invention also provides an amorphous bupropion hydrobromide granulate with al least one pharmaceutically acceptable carrier, processes for preparation thereof, and stable pharmaceutical compositions therewith.
2. Description of the Related Art
Bupropion is an antidepressant agent that is chemically distinct from tricyclic, tetracyclic and other commercially available antidepressants, e.g., selective serotonin-reuptake inhibitors, or “SSRIs.” m-chloro-α-(t-butylamino) propiophenone (herein “Bupropion”) has a CAS No. of 34911-55-2, described in U.S. Pat. Nos. 3,819,706 and 3,885,046, and is represented by the structure of Formula I:

Bupropion is the free base form of bupropion hydrobromide, which has a CAS number of 905818-69-1 and the following structure:

Bupropion hydrobromide was approved by the USFDA under the name APLENZIN® in the form of 174, 348, 522 mg tablets and is indicated for the treatment of major depressive disorder.
US Publication No. 2008051606 discloses three different crystalline polymorphic forms of bupropion hydrobromide named as Form-I, II, and III and can be characterized by powder X-ray powder diffraction pattern (PXRD).
The discovery of new amorphous forms of active pharmaceutical ingredients (“APIs”) provides opportunities to improve the performance characteristics, the solubility, stability, flowability, tractability and compressibility of drug substances and the safety and efficacy of drug products of a pharmaceutical product. Such discoveries enlarge the repertoire of materials that a formulation scientist has available for designing, for example, a pharmaceutical dosage form of a drug with a targeted release profile or other desired characteristic.
Generally, amorphous solids offer opportunities for solubility and bioavailability enhancement since these materials are more soluble than the crystalline form of the same compound. The rate of dissolution is also a consideration in formulating syrups, elixirs and other liquid medicaments.
Hence, it is desirable to provide methods of producing bupropion hydrobromide exhibiting enhanced bioavailability compared to the crystalline form of the compound. By converting a substantial portion of crystalline bupropion hydrobromide to the amorphous state, the aqueous solubility and bioavailability are increased. Furthermore, bupropion hydrobromide presented as an amorphous solid may facilitate manufacturing of both the active ingredient and the finished product and enable the use of reduced size dosage forms. Moreover, the selective customization of the properties of particles comprising bupropion hydrobromide can offer intriguing opportunities for pharmaceutical production and drug delivery. The morphology of individual particles plays a central role in this pursuit, since morphology directly influences bulk powder properties, such as density, residual solvent content, and flowability. In addition, techniques that modify particle shape and interior structure may profoundly affect pharmacokinetic properties, such as drug release rate, solubility, and bioavailability. Thus, the ability to design particle morphology has significant implications for the production process and product attributes.